IBX-mediated synthesis of indazolone via oxidative N–N bond formation and unexpected formation of quinazolin-4-one: in situ generation of formaldehyde from dimethoxyethane

• DOI: 10.1007/s12272-016-0706-z
• Publication Date: 2016-01-16T13:20:34Z
• Authors: Sang Won Park; Hoon Choi; Jung-hun Lee; Yeon-Ju Lee; Jin-Mo Ku; Sang Yeul Lee; Tae-gyu Nam
• Keywords: Ethyl Ethers; Indazoles; Cyclization; Formaldehyde; Benzoates; Oxidation-Reduction; 01 natural sciences; Iodine; Quinazolinones; 3. Good health; 0104 chemical sciences

Synthesis of indazolone derivatives, which exhibit diverse biological and pharmaceutical activities, were achieved by hypervalent λ(5) iodine reagents, such as iodoxybenzoic acid (IBX),-mediated oxidative N-N bond forming cyclization. In this study, the equivalence of IBX was optimized to promote the formation of N-N bond by oxidatively generated acylnitrenium ion. Dimethoxyethane and dichloroethane were discovered as alternative solvents and the reaction could be conducted in more concentrated condition. Some unprecedented substrates successfully afforded the corresponding indazolone in new condition discovered in this study. When the reactions were conducted in DME solvent, substrates with no electron-rich phenyl substituted amides afforded the unanticipated quinazolin-4-ones in moderate yields, which were not formed in DCE solvent. The formation of quinazolin-4-ones was attributed to the in situ generation of formaldehyde from DME. Therefore, the reaction might undergo different pathway in DME when the substrate aryl amides have phenyl rings without electron donating substituents.